Early CPAP as Effective For Preemies as Ventilator, With Fewer Complications

Two findings from an NIH research network study provide new information
on how much oxygen very preterm infants should receive starting on the
first day of life and the most effective means to deliver it to them.

The first was that higher oxygen levels improve preterm infants' survival
but increase the risk for a condition that can damage the retina.

The second was that a treatment typically used for adults with sleep
apnea also is as effective as the traditional ventilator and surfactant
therapy used to treat breathing difficulties in preterm infants — and
may result in fewer complications. The treatment relies on a continuous
positive airway pressure (CPAP) machine to blow air through a preterm
infantís nostrils, to gently inflate the lungs.

These findings appear in two articles published online by The New England
Journal of Medicine. The study results also will be presented on May
16 at the American Thoracic Society 2010 International Conference in
New Orleans.

"Until the current study, CPAP had shown promise in treating respiratory
distress in preterm infants, but had never been compared to ventilator
therapy in this group of patients," said Alan E. Guttmacher, M.D.,
acting director of the Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD), one of the NIH Institutes that
provided infrastructure and funding for the study. "The study results
indicate that CPAP is an effective initial alternative to ventilator
therapy for very preterm infants of 24-27 weeks gestational age."

The study was conducted by the 20 academic medical centers participating
in the NICHD's Neonatal Research Network. The study also received funding
from the NIH's National Heart, Lung, and Blood Institute.

The lead author of the article comparing oxygen saturation levels was
Waldemar A. Carlo, M.D., of the University of Alabama at Birmingham.
The lead author of the article comparing CPAP therapy to ventilator and
surfactant therapy was Neil N. Finer, M.D., of the University of California
at San Diego. The NICHD author of both papers was Rosemary D. Higgins,
M.D.

"Balancing the benefits of supplemental oxygen against the risks
in these very premature babies has been a concern of doctors and parents
for decades," said NHLBI Acting Director Susan B. Shurin, M.D.,
a board-certified pediatrician. "The results of this large clinical
trial of extremely low birthweight infants will help inform management
decisions to improve chances of survival and reduce complications associated
with breathing problems in these vulnerable patients."

The study enrolled 1,316 babies born between the 24th and 27th weeks
of pregnancy. A full-term pregnancy is 40 weeks long. The very premature
babies in the study had an average weight of less than two pounds.

The study was divided into two arms that provided the findings for the
articles. Each arm proceeded at the same time, in the same group of infants.
In the first arm, each infant had a 50 percent chance of receiving higher
oxygen target saturation levels, and a 50 percent chance of receiving
lower levels. In the second arm, each infant had a 50 percent chance
of receiving oxygen by CPAP and a 50 percent chance of receiving intubation
with surfactant, a viscous substance that helps keep the lungsí air sacs
open. Although surfactant normally is produced by the lung, premature
infants are not ready to make surfactant at first and suffer from severe
breathing difficulties.

Researchers Compare Higher Oxygen Levels To Lower Levels

Higher oxygen levels have been linked to an increase in the risk of
retinopathy of prematurity (ROP), a condition affecting the retina. The
current study was undertaken to determine if slightly reduced oxygen
levels would allow infants to remain healthy while reducing their risk
for ROP. Information on ROP (http://www.nei.nih.gov/health/rop/rop.asp)
is available from the National Eye Institute.

For the arm of the study that compared oxygen levels, the infants were
assigned at random to receive oxygen at one of two levels. The lower
level consisted of 85 to 89 percent oxygen saturation in the babies'
blood; the higher level 91 to 95 percent. The infants also were assigned
at random to receive oxygen either through a ventilator or a CPAP machine.

The researchers evaluated the infants at the two oxygen saturation levels
in a single combined measure, referred to as the combined outcome of
their survival and their likelihood of experiencing ROP. No overall difference
emerged between the groups in terms of this measure. However, there was
a striking difference when survival and likelihood of experiencing ROP
were considered separately.

More of the infants on the low oxygen level died than did infants on
the higher level: 19.9 percent compared to 16.2 percent. But among those
who survived, fewer on the lower level of oxygen developed ROP: 8.6 percent
versus 17.9 percent in the higher-oxygen group.

In this arm of the study, newborns who were randomly assigned to the
ventilator-surfactant treatment had a breathing tube placed in their
windpipes within an hour of birth and received a dose of surfactant.
Those who obtained CPAP treatment received oxygen through prongs placed
in their nostrils, also within the first hour of life. Any infant receiving
CPAP who subsequently did not achieve adequate oxygen levels in their
blood was placed on a ventilator. Of the infants who received CPAP treatment
initially, 83 percent required a ventilator tube in the windpipe and
67 percent received surfactant.

"Surfactant and intubation together have been shown to reduce the
risk of serious complications and death in preterm infants," Dr.
Finer said. "But the use of CPAP also grew during the last 10 or
15 years, without randomized studies to test it and compare it to surfactant."

The researchers looked at mortality and at a lung condition called bronchopulmonary
dysplasia, which is characterized by a need for oxygen therapy when the
baby is four weeks short of his or her original due date, or 36 weeks
after the motherís last menstrual period. When researchers compared CPAP
to surfactant on a combined measure of mortality and bronchopulmonary
dysplasia, the two types of breathing therapy were practically identical.

"The study shows that CPAP is an effective alternative to surfactant
in preterm infants," Dr. Higgins said. "Because it is less
invasive than ventilator therapy, CPAP appears to be an appropriate first
treatment for preterm newborns. If CPAP is unsuccessful, an infant can
be placed on a ventilator and given surfactant."

By other measures, children initially placed on CPAP actually fared
somewhat better than children who had received surfactant with the ventilator.
They were more likely to have survived and to not require breathing therapy
a week after being born. They were also less likely to need steroid treatment
for their lungs; and they spent less time overall on ventilators.

Furthermore, the earliest preterm infants in the study, born at 24 to
25 weeks gestation, were less likely to die if they had received CPAP
than if they had received surfactant as the initial treatment in the
study.

The team will evaluate the children again when they are 18 to 22 months
old, to learn whether any differences arise among the children who took
part in the different treatments arms of the study.

Part of the National Institutes of Health, the National Heart, Lung,
and Blood Institute (NHLBI) plans, conducts, and supports research related
to the causes, prevention, diagnosis, and treatment of heart, blood vessel,
lung, and blood diseases; and sleep disorders. The Institute also administers
national health education campaigns on women and heart disease, healthy
weight for children, and other topics. NHLBI press releases and other
materials are available online at http://www.nhlbi.nih.gov.

The NICHD sponsors research on development, before and after birth;
maternal, child, and family health; reproductive biology and population
issues; and medical rehabilitation. For more information, visit the Institute's
Web site at http://www.nichd.nih.gov/.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers
and is a component of the U.S. Department of Health and Human Services. NIH
is the primary federal agency conducting and supporting basic, clinical, and
translational medical research, and is investigating the causes, treatments,
and cures for both common and rare diseases. For more information about NIH
and its programs, visit http://www.nih.gov.